Daisuke Yoshino

Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21

Heartbeat is required for normal development of the heart, and perturbation of intracardiac flow leads to morphological defects resembling congenital heart diseases. These observations implicate intracardiac haemodynamics in cardiogenesis, but the signalling cascades connecting physical forces, gene expression and morphogenesis are largely unknown. Here we use a zebrafish model to show that the microRNA, miR-21, is crucial for regulation of heart valve formation. Expression of miR-21 is rapidly switched on and off by blood flow. Vasoconstriction and increasing shear stress induce ectopic expression of miR-21 in the head vasculature and heart. Flow-dependent expression of mir-21 governs valvulogenesis by regulating the expression of the same targets as mouse/human miR-21 (sprouty, pdcd4, ptenb) and induces cell proliferation in the valve-forming endocardium at constrictions in the heart tube where shear stress is highest. We conclude that miR-21 is a central component of a flow-controlled mechanotransduction system in a physicogenetic regulatory loop.

Design and Evaluation of Self-Expanding Stents Suitable for Diverse Clinical Manifestation Based on Mechanical Engineering

Atherosclerosis is one of the most prominent diseases that induce dysfunction of circulation, and it is a disease of large and medium size arteries. If cholesterol presenting at high concentration in a blood injures an intima, a white corpuscle, i.e. a monocyte, goes into the intima and mutates into a foam cell. Then, smooth muscle cells migrate from the media to the intima, and they grow proliferously there. Based on these phenomena, cholesterol and other lipid materials accumulate in the intima. Atherosclerosis has become a serious problem in the developed countries that are aging. Therefore, countermeasures to the atherosclerosis have become important. Although there are various medical treatments for the atherosclerosis, a stent placement has received much attention as a minimally invasive procedure for vascular stenotic lesion based on the coronary atherosclerosis, the arteriosclerosis obliterans, etc. A stent is a cylindrical tube-shaped medical device that can expand the stenotic lesion in a blood vessel continuously. When considering the expansion method of a stent, two types are available. One is a self-expanding type that can expand by itself when released from the sheath of a catheter. Another is a balloon-expandable type that must be expanded forcibly using a balloon catheter. Because the self-expanding stent continues to expand to the memorized diameter at the stenotic lesion, it has the long-term patency of a vascular wall. In the present study, the main target is the self-expanding type.

Local cyclical compression modulates macrophage function in situ and alleviates immobilization-induced muscle atrophy

Physical inactivity gives rise to numerous diseases and organismal dysfunctions, particularly those related to aging. Musculoskeletal disorders including muscle atrophy, which can result from a sedentary lifestyle, aggravate locomotive malfunction and evoke a vicious circle leading to severe functional disruptions of vital organs such as the brain and cardiovascular system. Although the significance of physical activity is evident, molecular mechanisms behind its beneficial effects are poorly understood. Here, we show that massage-like mechanical interventions modulate immobilization-induced pro-inflammatory responses of macrophages in situ and alleviate muscle atrophy. Local cyclical compression (LCC) on mouse calves, which generates intramuscular pressure waves with amplitude of 50 mmHg, partially restores the myofiber thickness and contracting forces of calf muscles that are decreased by hindlimb immobilization. LCC tempers the increase in the number of cells expressing pro-inflammatory proteins, tumor necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1), including macrophages in situ The reversing effect of LCC on immobilization-induced thinning of myofibers is almost completely nullified when macrophages recruited from circulating blood are depleted by administration of clodronate liposomes. Furthermore, application of pulsatile fluid shear stress, but not hydrostatic pressure, reduces the expression of MCP-1 in macrophages in vitro Together with the LCC-induced movement of intramuscular interstitial fluid detected by µCT analysis, these results suggest that mechanical modulation of macrophage function is involved in physical inactivity-induced muscle atrophy and inflammation. Our findings uncover the implication of mechanosensory function of macrophages in disuse muscle atrophy, thereby opening a new path to develop a novel therapeutic strategy utilizing mechanical interventions.

Characteristics of plasma in culture medium generated by positive pulse voltage and effects of organic compounds on its characteristics

We describe a positive pulse voltage method for generating plasma in culture medium with a composition similar to biological fluids. We also describe the plasmas characteristics, liquid quality, and the effect of organic compounds in the culture medium on the plasma characteristics through comparisons to a solution containing inorganic salts at the same concentrations as in the culture medium. Light emission with Na and OH spectra was observed within a vapor bubble produced by Joule heating at the tip of the electrode. A downward thermal flow and shock wave were caused by the behavior of the vapor bubble. The culture medium pH gradually increased from 7.9 to 8.3 over the discharge time of 300 s. H2O2 was generated 1.1 mg l−1 in the culture medium after discharge for 300 s, and this value was 0.5 mg l−1 lower than the inorganic salts solution which does not contain organic compounds. This study provides important data that will help facilitate more widespread application of plasma medicine.